When antiretroviral therapy (ART) fails to suppress HIV replication, drug resistance can develop and be transmitted. This can be particularly devastating in resource limited settings where only a few ART regimens are available. The overarching aims of this proposal are to enhance a productive collaboration between UCSD and investigators in Chennai, India and to evaluate unique cost-containing methods for viral load monitoring of Indian patients on first-line ART. Specifically, we will enroll 500 HIV-infected patients followed at a HIV clinic in Chennai, India for monitoring of virologic failure of first-line ART. We will evaluate three approaches of nucleic acid testing (NAT) for HIV RNA: 1) individual samples, 2) minipools of 5 samples, and 3) 10x10 sample pooling matrix. Innovatively, the pooling methods make use of the quantitative information that is available from the viral loads to identify individual samples with virologic failure within the platforms of pooled samples. We will define the test characteristics of each method including: accuracy, efficiency, result turn-around time and costs, and we will determine if simple adherence measures can improve these test characteristics. These experiments will also allow us to define the prevalence of virologic failure in this study population group. Taken together, the generated data will serve as the basis for choosing a sustainable method for monitoring for virologic failure in Southern India. PUBLIC HEALTH RELEVANCE: We still struggle with availability of effective antiretroviral therapy and CD4 monitoring in most parts of the world where most of the people infected with HIV live. In these settings, the availability of viral load monitoring is practically unattainable for the vast majority of patients, often because of the lack of infrastructure and technical expertise. Even when infrastructure and expertise exist, cost prohibits its use. We propose in this application to evaluate the test characteristics of novel methods that may ultimately bring viral load monitoring to resource-limited settings.